Immunohistochemical detection and quantitation of P-glycoprotein in multiple drug-resistant human myeloma cells: Association with level of drug resistance and drug accumulation

W. S. Dalton, T. M. Grogan, J. A. Rybski, R. J. Scheper, L. Richter, J. Kailey, H. J. Broxterman, H. M. Pinedo, S. E. Salmon

Research output: Contribution to journalArticlepeer-review

Abstract

Using several multiple drug-resistant human myeloma cell lines as standards, we developed an immunohistochemical staining technique and means of quantitating P-glycoprotein in individual myeloma cells. The level of staining intensity of P-glycoprotein in individual myeloma cells was quantitated by measuring the average optical density of each cell with a microscopic computerized cell analysis system. Using this system, we observed that the level of P-glycoprotein for individual cells within a cell population of known drug sensitivity was very homogeneous (coefficient of variation, ≤ 13%). Analysis of cell lines with gradually increasing levels of multidrug resistance (8226/S, 8226/Dox6 and 8226/Dox40) demonstrated a close association between the level of resistance to doxorubicin, defined by the mean lethal dose (D0) and the amount of P-glycoprotein on individual cells determined by the optical density (r = 0.82, P <0.0005). Intracellular doxorubicin (DOX) accumulation in the individual cell lines was inversely related to the level of drug resistance expressed as D0. P-glycoprotein was also detected in the marrow-derived myeloma cells of patients with drug refractory disease using immunohistochemical staining. The amount of P-glycoprotein in the cells of one patient was directly compared to the amount found in the simultaneously stained standard cell lines (8226/Dox6 and 8226/Dox40) by comparing the optical densities for individual cells. Using this immunohistochemical technique to detect and quantitate P-glycoprotein in patient myeloma cells and comparing it to standard multidrug resistant myeloma cell lines may be of value in determining the contribution of P-glycoprotein to clinical drug resistance in patients with multiple myeloma.

Original languageEnglish (US)
Pages (from-to)747-752
Number of pages6
JournalBlood
Volume73
Issue number3
StatePublished - 1989
Externally publishedYes

ASJC Scopus subject areas

  • Hematology

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